Inhibitory effect of angiotensin II receptor antagonist on hepatic stellate cell activation in non-alcoholic steatohepatitis

Yokohama, Shiro; Tokusashi, Yoshihiko; Nakamura, Kimihide; Tamaki, Yosui; Okamoto, Satoshi; Okada, Mituyoshi; Aso, Kazunobu; Hasegawa, Toshiyuki; Aoshima, Masaru; Miyokawa, Naoyuki; Haneda, Masakazu; Yoneda, Masashi

doi:10.3748/wjg.v12.i2.322

Cited by 91 publications

(69 citation statements)

References 22 publications

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“…In 2004, a clinical pilot study revealed the beneficial efficacy of losartan, one of the ARBs, against NASH by evaluating serum biochemical indices and hepatic histology [96]. Moreover, the effect of ARB on NASH was shown to be through the inhibition of activated hepatic stellate cells in NASH patients [97]. After this pilot study, many animal and in vitro studies confirmed the beneficial efficacy of ARBs against NASH, but clinical studies were very limited.…”

Section: Metformin Cq: Are Biguanides Effective For Patients With Nafmentioning

confidence: 84%

Evidence-based clinical practice guidelines for nonalcoholic fatty liver disease/nonalcoholic steatohepatitis

et al. 2015

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Nonalcoholic fatty liver disease (NAFLD) is currently the most common cause of chronic liver disease in industrialized countries worldwide, and has become a serious public health issue not only in Western countries but also in many Asian countries including Japan. Within the wide spectrum of NAFLD, nonalcoholic steatohepatitis (NASH) is a progressive form of disease, which often develops into liver cirrhosis and increases the risk of hepatocellular carcinoma. In turn, a large proportion of NAFLD/NASH is the liver manifestation of metabolic syndrome, suggesting that NAFLD/NASH plays a key role in the pathogenesis of systemic atherosclerotic diseases. Currently, a definite diagnosis of NASH requires liver biopsy, though various noninvasive measures are under development. The mainstays of prevention and treatment of NAFLD/NASH include dietary restriction and exercise; however, pharmacological approaches are often necessary.Currently, vitamin E and thiazolidinedione derivatives are the most evidence-based therapeutic options, although the clinical evidence for long-term efficacy and safety is limited. This practice guideline for NAFLD/NASH, established by the Japanese Society of Gastroenterology in cooperation with The Japan Society of Hepatology, covers lines of clinical evidence reported internationally in the period starting from 1983 to January 2012, and each clinical question was evaluated using the GRADE system. Based on the primary release of the full version in Japanese, this English summary provides the core essentials of this clinical practice guideline comprising the definition, diagnosis, and current therapeutic recommendations for NAFLD/NASH in Japan.

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Section: Metformin Cq: Are Biguanides Effective For Patients With Nafmentioning

confidence: 84%

Evidence-based clinical practice guidelines for nonalcoholic fatty liver disease/nonalcoholic steatohepatitis

et al. 2015

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“…The effects of Ang II on hepatic stellate cells (HSC) has been extensively studied (Bataller et al 2005(Bataller et al , 2003a(Bataller et al , b, 2000Wei et al 2001;Yokohama et al 2006;Zhang et al 2003), yet little information exists on the effect of Ang-(1-7) on these cells. Most studies using cell culture use culture medium supplemented with fetal calf serum (FCS) to encourage cell growth.…”

Section: Introductionmentioning

confidence: 99%

Angiotensin converting enzyme 2 (ACE2) activity in fetal calf serum: implications for cell culture research

et al. 2008

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Cell culture experiments often employ the use of culture media that contain fetal calf serum (FCS). The angiotensin peptides angiotensin II and angiotensin 1-7 have opposing effects with angiotensin converting enzyme 2 (ACE2) being the enzyme predominantly responsible for generating angiotensin 1-7 from angiotensin II. The effect of FCS on angiotensin peptides has not previously been described. We have shown that FCS has ACE2 enzyme activity capable of degrading angiotensin II and generating angiotensin 1-7. Researchers should be aware that FCS possesses ACE2 activity and that heat-treating FCS to 56°C only partially inhibits this enzyme activity, whereas heat-treating to 70°C completely abolishes ACE2 activity.

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“…AT-1 receptor antagonists including captopril, candesartan and losartan inhibit liver fibrosis in bile duct-ligated and CCl 4 treated rats (255)(256)(257). In human studies, it is suggested that AT-1 receptor antagonist can decrease the number of activated HSCs (258). A controlled pilot study in hepatitis C showed that losartan reduces liver fibrosis as compared to untreated controls (259) ET-1 is another vasoconstrictor that merits study.…”

Section: Modulation Of Vasoactivementioning

confidence: 99%

Bioconjugation of Oligonucleotides for Treating Liver Fibrosis

Houssein

Mahato

2007

Oligonucleotides

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Liver fibrosis results from chronic liver injury due to hepatitis B and C, excessive alcohol ingestion, and metal ion overload. Fibrosis culminates in cirrhosis and results in liver failure. Therefore, a potent antifibrotic therapy is in urgent need to reverse scarring and eliminate progression to cirrhosis. Although activated hepatic stellate cells (HSCs) remains the principle cell type responsible for liver fibrosis, perivascular fibroblasts of portal and central veins as well as periductular fibroblasts are other sources of fibrogenic cells. This review will critically discuss various treatment strategies for liver fibrosis, including prevention of liver injury, reduction of inflammation, inhibition of HSC activation, degradation of scar matrix, and inhibition of aberrant collagen synthesis. Oligonucleotides (ODNs) are short, single-stranded nucleic acids, which disrupt expression of target protein by binding to complementary mRNA or forming triplex with genomic DNA. Triplex forming oligonucleotides (TFOs) provide an attractive strategy for treating liver fibrosis. A series of TFOs have been developed for inhibiting the transcription of α1(I) collagen gene, which opens a new area for antifibrotic drugs. There will be in depth discussion on the use of TFOs and how different bioconjugation strategies can be utilized for their site-specific delivery to HSCs or hepatocytes for enhanced antifibrotic activities. Various insights developed in individual strategy and the need for multipronged approaches will also be discussed.

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Inhibitory effect of angiotensin II receptor antagonist on hepatic stellate cell activation in non-alcoholic steatohepatitis

Abstract: Our data suggest the crucial involvement of HSCs in anti-fibrotic effect of angiotensin II receptor antagonist on patients with NASH.

Cited by 91 publications

References 22 publications

Evidence-based clinical practice guidelines for nonalcoholic fatty liver disease/nonalcoholic steatohepatitis

Evidence-based clinical practice guidelines for nonalcoholic fatty liver disease/nonalcoholic steatohepatitis

Angiotensin converting enzyme 2 (ACE2) activity in fetal calf serum: implications for cell culture research

Bioconjugation of Oligonucleotides for Treating Liver Fibrosis

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